Table 3 Characteristics of included RCT

Britton 1987 [58]

RCT

To study the effectiveness of high-dose ASA after cerebral infarction

ASA 1.5 g/d vs placebo

N = 505, mean age 68 years

2 years

Primary outcomes: Recurrent stroke or death. Secondary outcomes: myocardial infarction, TIA

Diener 2004 [53]

RCT

To assess whether addition of ASA to clopidogrel could have a greater benefit than clopidogrel alone in prevention of vascular events with potentially higher bleeding risk

ASA 75 mg/d + clopidogrel 75 mg/d vs placebo + clopidogrel 75 mg/d

N = 7599, placebo + clopidogrel: mean age 66.1 years, 54% older than 65 years. ASA + clopidogrel: mean age 66.5 years, 56% older than 65 years. Subgroup analysis age ≥ 65 years

18 months

Primary outcomes: composite of ischaemic stroke, myocardial infarction, vascular death or rehospitalisation for an acute ischaemic event. Secondary outcomes: Individual and various combinations of each of the outcomes forming the primary endpoint, any death, any stroke

EAFT 1993 [34]

RCT

To assess the preventive benefit of anticoagulation or ASA in patients with recent transient ischaemic attack or minor ischaemic stroke

ASA 300 mg/d vs OAC INR 2.5–4.0 vs placebo

N = 1007, OAC: mean age 71 years. 80% older than 65 years. ASA: mean age 73 years, 84% older than 65 years. Placebo: mean age 73 years, 84% older than 65 years

2.3 years

Primary outcomes: death from vascular disease, non-fatal stroke (including haemorrhage), non-fatal myocardial infarction or systemic embolism. Secondary outcomes: death from all causes, all strokes, major thromboembolic events

Huynh 2001 [36]

RCT

To test the hypothesis that moderate-intensity warfarin either alone or in combination with low-dose ASA will be more effective than ASA alone for the secondary prevention of coronary events in patients with previous CABG

ASA 80 mg/d + placebo, warfarin INR 2–2.5 + placebo, ASA 80 mg/d + warfarin INR 2–2.5

N = 135, ASA + placebo: mean age 68, 61% older than 65 warfarin + placebo: mean age 67, 57% older than 65, ASA + warfarin: mean age 66, 53% older than 65 years. Subgroup analysis age ≥ 65 years

12 months

Primary outcomes: composite end point of any-cause death, myocardial infarction, unstable angina requiring a new hospitalization. Secondary outcome: performance of reperfusion procedure (either percutaneous or open chest)

Ikeda 2014 [35]

RCT

To determine whether daily low-dose ASA reduces the incidence of cardiovascular events in older Japanese patients with multiple atherosclerotic risk factors

ASA 100 mg/d vs control

N = 14,464, ASA: mean age 70.6, 82% older than 65. Control: mean age 70.5, 81% older than 65

5.02 years

Primary outcome: composite of death from cardiovascular causes, non-fatal stroke and non-fatal myocardial infarction. Secondary outcomes: composite of primary outcomes + TIA, angina pectoris and arteriosclerotic disease requiring surgery or intervention; death from cardiovascular causes, non-fatal stroke, non-fatal myocardial infarction, TIA, angina pectoris, arteriosclerotic disease requiring surgery or intervention, serious extracranial haemorrhage

Kjeldsen 2000 (HOT) [31]

RCT

To study the relationship between three levels of target diastolic blood pressure and cardiovascular events in hypertensive patients and to examine the effects of 75 mg ASA daily versus placebo

ASA 75 mg/d

N = 18,790; men: mean age 60.8 years, 28% older than 65 years. Women: mean age 62.3 years, 36% older than 65 years. Subgroup analysis age ≥ 65 years

3.8 years

Major CV events, MI, Stroke CV mortality, total mortality

Liu 2014 [47]

RCT

To compare the therapeutic warfarin and ASA efficacies for treatments of atrial fibrillation complicated with stable coronary heart disease

Warfarin INR 1.6–2.5, ASA 100 mg/d

N = 101, warfarin: mean age 84.8 years, ASA: mean age 84.4 years. 100% older than 65 years

2 years

Primary outcome: ischaemic stroke, systemic embolism. Secondary outcomes: non-fatal myocardial infarction and all causes of death

Ogawa 2008 [33]

RCT

To examine the efficacy of low-dose ASA for the primary prevention of atherosclerotic events in patients with type 2 diabetes

ASA 81–100 mg/d vs control

N = 2539, mean age 65 years. ASA: 50% older than 65 years. Non-ASA group: 46% older than 65 years. Subgroup analysis age ≥ 65 years

4.37 years

Primary outcomes: Any atherosclerotic event (composite endpoint of sudden death, death from coronary, cerebrovascular, and aortic causes, non-fatal acute myocardial infarction, unstable angina, newly developed exertional angina, non-fatal ischaemic and haemorrhagic stroke, transient ischaemic attack, non-fatal aortic and peripheral vascular disease). Secondary outcomes: each primary endpoint and combinations of primary endpoints, death from any cause

Silagy 1993 [32]

RCT

To investigate the incidence of adverse effects resulting from the use of regular low-dose ASA in an otherwise healthy elderly population

ASA 100 mg/d vs placebo

N = 400, mean age 73 years, 100% older than 65 years

12 months

Adverse events (gastrointestinal symptoms, gastrointestinal bleeding, easy bruising, nose bleeds), haematologic parameters

Uchiyama 2016 [50]

RCT

To evaluate the effect of ASA on the risk of stroke and intracranial haemorrhage in the Japanese Primary Prevention Project.

ASA 100 mg/d vs control

N = 14,464, ASA: mean age 70.6 years, 82% older than 65 years. No ASA: 70.5 years, 81% older than 65 years

5.02 years

Primary outcomes: composite of death from cardiovascular causes (including fatal myocardial infarction, fatal stroke, and other cardiovascular death), non-fatal stroke and non-fatal MI. Secondary outcomes: composite of the same events as the primary end points plus TIA, angina pectoris and atherosclerotic disease requiring surgery or intervention. Death from cardiovascular disease, death from nonvascular causes, non-fatal stroke, non-fatal MI, TIA, angina pectoris, atherosclerotic disease requiring surgery or intervention, serious extracranial haemorrhage requiring transfusion or hospitalization.

Wiviott 2007 [51]

RCT

To compare prasugrel with clopidogrel for the prevention of thrombotic complications in patients with an acute coronary syndrom and scheduled percutaneous coronary intervention

Prasugrel 60 mg loading-dose, 10 mg daily maintenance dose vs clopidogrel 300 mg loading-dose, 75 mg daily maintenance

N = 13,608, mean age 61 years. Subgroup analysis age ≥ 65 years.

6–15 months

Primary outcomes: composite of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke. Secondary outcomes: stent thrombosis and a composite of death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, or rehospitalisation due to a cardiac ischaemic event. Safety outcomes: major bleeding not related to coronary-artery bypass grafting, life threatening bleeding not related to coronary-artery bypass grafting, major and minor bleeding